Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Standard loco-regional treatment without prophylactic contralateral breast irradiation

Standard loco-regional treatment with prophylactic contralateral breast irradiation

The whole contralateral breast will be irradiated once daily, 5 days a week, for 5-6 weeks, using 1.8-2 Gy/fx to a total dose of 45-50 Gy.

Prophylactic contralateral breast irradiation

Yiding Chen, M.D.

Jiaojiao Zhou

Zhengkui Sun, M.D.

Kejin Wu, M.D.

Xiaowen Ding, M.D.

Peifen Fu, M.D.

Weijun Cjen, M.D.

Zhibing Wu

Mikael Hartman

Wenjun Chen, M.D.

Zhengkui Sun

Yiding Chen

Kun Zhang

Wenhong Xu

Breast cancer is the most common cancer in women worldwide, with high mortality. About 5% to 10% of breast cancers are hereditary. Most inherited cases of breast cancer are associated with germline mutations in genes, such as BRCA1, BRCA2 and PALB2. The cumulative breast cancer risk for BRCA1, BRCA2 or PALB2 mutation carriers was high.

Besides the increased breast cancer risk for the inherited mutation carriers, the risk of subsequent contralateral breast cancer for the mutation carriers with breast cancer was also significantly increased. Contralateral prophylactic mastectomy was usually recommended to the breast cancer patients with BRCA mutation. However, many breast cancer patients refused the contralateral prophylactic mastectomy, due to the surgical injury, potential surgical complications, deleteriously affected body image and sexuality.

Solid evidence validated that radiotherapy after surgery resulted in a reduced local recurrence for three times lower than surgery alone. It is thought that radiation would eliminate the microscopic tumors which may already exist in the breast. Thus, we proposed that for the breast cancer patients with BRCA1, BRCA2 or PALB2 deleterious germline mutations, prophylactic irradiation to the contralateral breast may reduce the risk of subsequent contralateral breast cancer. And we would like to further compare the effect of prophylactic irradiation to the published data from traditional prophylactic contralateral mastectomy.

Breast cancer is the most common cancer in women worldwide, with high mortality. In the US in 2018, the number of estimated new cases of breast cancer accounted for 30% of all the new cancer cases in women, while the estimated deaths of breast cancer accounted for 14% of all new cancer deaths. In Chinese females, the most commonly diagnosed cancer was breast cancer, accounting for 19% of total cases. And breast cancer was the main 5 most common causes of cancer-related deaths in China.

About 5% to 10% of breast cancers are hereditary. Most inherited cases of breast cancer are associated with germline mutations in two genes: BRCA1 (BRCA1 DNA repair associated) and BRCA2 (BRCA2 DNA repair associated). The cumulative breast cancer risk for BRCA1 or BRCA2 mutation carriers at age 70 years reached as high as 50% in US population and 37% in Chinese population. Benefiting from the next generation sequencing technology, more inherited gene mutations were discovered. Among these new discovered susceptibility genes, PALB2 (Partner and localizer of BRCA2) was associated with high increased risks of breast cancer in both Chinese and US population.

Besides the increased breast cancer risk for the inherited mutation carriers, the risk of subsequent contralateral breast cancer for the mutation carriers with breast cancer was also significantly increased. For contralateral breast cancer in BRCA mutation carriers, the cumulative risk for 10 years after breast cancer diagnosis was as high as 25% and for 20 years reached to 40%, as compared 3% and 12% respectively in non-carriers. Contralateral prophylactic mastectomy was usually recommended to the breast cancer patients with BRCA mutation, as it can absolutely reduce the risk of contralateral primary cancer. However, many breast cancer patients refused the contralateral prophylactic mastectomy, due to the surgical injury, potential surgical complications, deleteriously affected body image and sexuality.

Solid evidence validated that radiotherapy after surgery resulted in a reduced local recurrence for three times lower than surgery alone. It is thought that radiation would eliminate the microscopic tumors which may already exist in the breast. Thus, we proposed that for the breast cancer patients with BRCA1, BRCA2 or PALB2 deleterious germline mutations, prophylactic irradiation to the contralateral breast may reduce the risk of subsequent contralateral breast cancer. And we would like to further compare the effect of prophylactic irradiation to the published data from traditional prophylactic contralateral mastectomy.

Prophylactic Irradiation to the Contralateral Breast for BCAs Patients

Phase II Multicenter Clinical Trial of Prophylactic Irradiation to the Contralateral Breast for Breast Cancer Patients With BRCA1, BRCA2 and PALB2 Deleterious Mutation

The recurrence rate of contralateral breast cancer

The length of time from either the date of diagnosis or the start of lumpectomy or mastectomy for primary breast cancer with or without prophylactic irradiation to the contralateral breast

Reappearance of cancer in the ipsilateral preserved breast, chest wall, axillary or supraclavicular lymph nodes.

Breast cancer that has spread from the original (primary) breast cancer to distant organs or distant lymph nodes.

Any short term adverse effects that related to prophylactic irradiation

Any long term adverse effects that related to prophylactic irradiation

Second Affiliated Hospital, School of Medicine, Zhejiang University

Symptoms and General Pathology

Genetic Predisposition to Disease

Disease Susceptibility

Disease Attributes

The saliva samples will be made of selected related (DNA).

salivary kit

Sandrine CAPUTO, PhD

Isabelle TURBIEZ, Project Manager

Emmanuelle FOURME, PhD

Emmanuelle FOURME, MD

Dominique STOPPA-LYONNET, PU-PH

Gilles MORIN, MD

Marie COUDERT, MD

Stéphanie CHIEZE-VALERO, MD

Hélène DREYFUS, MD

Marie-Agnès COLLONGE-RAME, MD

Julie TINAT, MD

Virginie BUBIEN, MD

Isabelle MORTEMOUSQUE, MD

Marc PLANES, MD

Pascaline BERTHET, MD

Sandra FERRER, MD

Mathilde GAY-BELLILE, MD

Jean-Marc LIMACHER

Jean-Marc LIMACHER, MD

Laurence FAIVRE-OLIVIER, MD

Clémentine LEGRAND, MD

Elodie LACAZE, MD

Audrey MAILLIEZ, MD

Sophie LEJEUNE, MD

Laurence VENAT-BOUVET, MD

Sophie GIRAUD, MD

Christine LASSET, MD

Hagay SOBOL, PhD

Hélène ZATTARA, MD

Isabelle COUPIER, MD

Alain LORTHOLARY, MD

Véronique MARI, MD

Jean CHIESA, MD

E COTTEREAU, MD

Antoine DARDENNE, MD

Véronica CUSIN, MD

Clémence EVREVIN, MD

Odile COHEN-HAGUENAUER, MD

Pierre-Laurent PUIG, Phd

Anne DURLACH, MD

Fanny BRAYOTEL, MD

Tan Dat NGUYEN, PHD

Louise CRIVELLI, MD

Isabelle TENNEVET, MD

Capucine DELNATTE, MD

Fabienne PRIEUR, MD

Philippe BOUDIER, MD

Christine MAUGARD, MD

Laurence GLADIEFF, MD

Charlotte CAILLE-BENIGNI, MD

Marie-Noëlle BONNET-DUPEYRON, MD

Jean-Marie RAVEL, MD

Olivier CARON, MD

Marilyn LACKMY-PORT-LIS, MD

Odile BERA, MD

Hanitra RANJATOELINA, MD

The aim of the COVAR project is to classify reliably a maximum of VUS of the French database in order to use them for the genetic counseling. The results obtained through this study will have a major impact on clinical management of the patients and their families conducting in some cases to propose a prophylactic surgery.

Originally, the COVAR study was designed to explore Variants of unknown biological significance (VUS) in BRCA1 (BReast Cancer 1) and BRCA2 (BReast Cancer 2) genes, which are the two major genes identified in hereditary breast and/or ovarian cancers. Since then the study has evolved, in parallel with the evolution of diagnosis, first introducing the PALB2 (Partner and localizer of BRCA2) gene explored in diagnosis since 2015 and now opening the study to all the genes of the panels performed in diagnosis in families with a genetic predisposition syndrome to cancers.

The French UMD (Universal Mutation Database)-BRCA1/2, accredited by the French National Cancer Institute, collects anonymous results of genetic tests performed by authorized French laboratories since 1995, giving a real-time vision of families carrying the same VUS. In september 2011, the French UMD-BRCA1/2 database comprised 706 different variants in 1,300 BRCA1 families and 1,089 different variants in 2,101 BRCA2 families. In April 2021, this database contained 1,651 different VSU for BRCA1, 3,015 different VUS for BRCA2, 471 different VUS for PALB2, 68 for RAD51C and 66 for RAD51D.

Since 2017, new genes have been explored in the diagnostic setting as they have been reported as predisposing factors for cancers. This list is constantly evolving (Moretta et al., 2018; Dhooge et al., 2020). Data collection for these genes is ongoing and a new database (FrOG) gathering all VUS and mutations identified in the French oncogenetic network has been set up. We have set up a consortium agreement at the end of 2020. This database gathers to date 12 genes and 11,912 different variants in more than 40,000 French families.

One of the key measurable parameters for classification of VUS as causal mutations is their co-segregation with the disease. The average size of French families is relatively small, the information of variant co-segregation limited to one family would not be significant. However, the compilation of co-segregation results obtained from several families will allow to obtain more precise and complete estimations of the probability of causality of a given variant.

The objective of the COVAR study (COsegregation VARiants) is to organize co-segregation studies of the VUS of the database UMD-BRCA1/2, in order to determine the causal or non-causal nature of these variants. To organize the variants by their clinical relevance, a grid with 5 classes has been used: 1=neutral, 2=likely neutral, 3=VUS, 4=likely causal, 5=causal. The VUS of classes 3 and 4 will be candidates to co-segregation studies because they cannot be used for the genetic counseling.

In the selected families the index case will invite the family members (affected and unaffected) to provide a sample of salivary fluid to test the presence of the VUS. The probability that a VUS is causal will be calculated from the cosegregation data using a Bayesian model. The results will be integrated in the multifactorial model described by D. Goldgar, model integrating different parameters as amino acid conservation, structural impact of the variant, co-occurrence with a pathogenic mutation, family history and tumor characteristics.

COsegregation of VARiants in Panel of Genes

Study of Family COsegregation of Nucleotide VARiants in the Panel of Genes to Validate Their Use in Genetic Counseling

Institut Curie

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

The exposition to the primary analysis risk factor (germline deleterious mutation in BRCA1, BRCA2, ATM or PALB2 gene) will be determined after inclusion. Briefly, a NGS targeted-panel based on the majority of genes included in the BROCA panel and additional DNA-repair related genes has been designed based on the available technology. The pathogenicity of germline variants will be determined according to established American College of Medical Genetics and Genomics and Association for Molecular Pathology current consensus at the time of final primary outcome analyses. Variants will also be reviewed against published literature and public databases. According to their mutation-carrier status patients will be classified as: A) Mutation Carriers in BRCA1, BRCA2, ATM and PALB2 genes; B) Mutation carriers in other genes included in the BROCA panel; C) Mutation carriers in others DNA-repair genes D)Non-carriers

David Olmos, MD

PROREPAIR is a prospective multicenter observational cohort study of unselected patients with metastatic Castration Resistant Prostate Cancer (mCRPC) with unknown germline mutational status at study entry and who are candidates to start 1st line treatment with any approved survival-prolonging agent.

The study aims to evaluate the impact of aberrations in DNA-repair genes,(BRCA1, BRCA2, ATM and PALB2 and other genes) on cause-specific survival from the diagnosis of the metastatic castration resistant status and other outcomes.

This is a non-interventional study in which eligible patients are prospectively followed-up until death or the end-of-study, whichever happens first.

Patients are enrolled after mCRPC diagnosis and before or within the 6 first months of starting a first-line treatment with any approved survival-prolonging agent for mCRPC. First and subsequent treatment lines will be chosen according to the patients and their treating physicians preferences and will not be dictated by this study.

A whole blood sample for germline DNA extraction as well as any available archival prostate cancer tissue samples will be collected at baseline. Optional plasma, serum and whole blood samples will be collected at baseline and at different time points along the evolution of the disease. A sample will be collected within the last 6 months of life.

Survival and treatment outcomes including biochemical, radiological and clinical progression with standard approved agents abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223 will be prospectively collected.

Primary aim is to evaluate the prevalence and impact of DNA repair germline mutations in the BRCA1, BRCA2, ATM and PALB2 genes on cause-specific survival from mCRPC. Secondary aims will include the correlation of additional germline alterations in DNA-repair with survival and treatment outcomes; the analyses of the survival and treatment outcomes impact of somatic alterations in these genes and the role of germline and somatic defects in the clonal evolution of prostate cancer.

Whole blood, plasma, serum, archival FFPE and fresh tumour samples

Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)

Prospective Multicentre Cohort Study of the Prevalence and Clinical Impact of Germline Deleterious Mutations in DNA Repair Genes of Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

To assess the impact of BRCA1, BRCA2, ATM, PALB2 germline mutations on cause-specific survival from diagnosis of metastatic castration resistance status.

To analyze the impact of other germline mutations in other DNA repair genes on cause-specific survival from diagnosis of metastatic castration resistance

To explore the correlation between DNA repair germline mutation carrier status and cause-specific survival following first, second, third and successive treatment lines.

To study the correlation between BRCA1, BRCA2, ATM, PALB2 and other genes mutation carrier status and the biochemical response and time to biochemical progression following treatment with abiraterone acetate, enzalutamide, radium-223, docetaxel and/or cabazitaxel.

To study the correlation between BRCA1, BRCA2, ATM, PALB2 and other genes mutation carrier status and the radiographic response and time to radiographic progression following treatment with abiraterone acetate, enzalutamide, radium-223, docetaxel and/or cabazitaxel.

To explore in this cohort the correlation between somatic DNA repair abnormalities with cause-specific survival and other treatment-related outcomes.

To correlate DNA repair somatic and germline alterations with prior prostate cancer history characteristics and established risk factors.

Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

Instituto de Investigacion Biomedica de Malaga

Centro Nacional de Investigaciones Oncologicas CARLOS III

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Rare Diseases

Uterine Cervical Neoplasms

Esophageal Neoplasms

Carcinoma

Pancreatic Neoplasms

Stomach Neoplasms

Sarcoma

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Urinary Bladder Neoplasms

Carcinosarcoma

Mixed Tumor, Mullerian

Leiomyosarcoma

Esophageal Cancer

Pancreatic Cancer

Ovarian Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Fallopian Tube Cancer

Malignant Mixed Mullerian Tumor

Antineoplastic Agents

All Drugs and Chemicals

Herbal and Botanical

Poly(ADP-ribose) Polymerase Inhibitors

Rucaparib

Enzyme Inhibitors

Cola

Eligible participants will be enrolled in either Cohort A or Cohort B.

Cohort A: Up to 200 participants with deleterious mutations in BRCA1, BRCA2, PALB2, RAD51C or RAD51D.

Cohort B (Exploratory): Up to 20 participants with deleterious mutations in BARD1, BRIP1, FANCA, NBN, RAD51 or RAD51B.

Oral rucaparib will be administered twice daily. The starting dose will be 600 mg daily (BID).

Kim Reiss-Binder, MD

A Phase 2, open-label, single-arm trial to evaluate the response of rucaparib in participants with various solid tumors and with deleterious mutations in Homologous Recombination Repair (HRR) genes.

A Study to Evaluate Rucaparib in Participants With Solid Tumors and With Deleterious Mutations in HRR Genes

A Phase 2 Multicenter, Open-label Study of Rucaparib as Treatment for Solid Tumors Associated With Deleterious Mutations in Homologous Recombination Repair Genes

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations.

Data will be provided by Clovis Oncology.

Best overall response rate as assessed by the investigator by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in participants with advanced prostate cancer).

Best overall response rate by independent radiology review by RECIST v1.1 (or by RECIST v1.1 and PCWG3 in participants with advanced prostate cancer).

Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression.

Measure of clinical benefit, defined as the percentage of complete response (CR), partial response (PR), and stable disease (SD) beyond 16 weeks.

Measure of clinical benefit, defined as the duration from study enrollment to objective tumor progression. Progression was defined using RECIST v1.1, as a 20% increase in the sum of diameters of target lesions (and an absolute increase of at least 5 mm), or unequivocal progression of existing non-target lesions, or the appearance of new lesions. For mCRPC disease, the PCWG3 confirmed bone disease progression criteria (2+2) were also incorporated.

Measure of clinical benefit, defined as the duration from study enrollment to death.

pharmaand GmbH

Adverse events are reported for the Safety Population, defined as participants who received at least one dose of protocol-specified treatment.

Participants with a deleterious mutation in one of the following genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.

Rucaparib Cohort A

Participants with a deleterious mutation in one of the following genes: BARD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.

Rucaparib Cohort B

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Kim Reiss Binder

Efficacy population - all participants evaluable for response by RECIST v1.1 (or modified RECIST v1.1/PCWG3 for mCRPC participants).

Best Overall Response Rate by Investigator

No data were collected as the independent radiology review was not performed.

Overall Response Rate by Independent Radiology Review

Participants with a deleterious mutation in one of the following genes: BRD1, BRIP1, FANCA, NBN, RAD51, or RAD51B.

Duration of Response

Disease Control Rate

Safety Population - all enrolled participants who received at least 1 dose of protocol-specified treatment.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prophylactic Irradiation to the Contralateral Breast for BCAs Patients	NCT04960839	Breast Cancer	Prophylactic co...	30 Years - 70 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
COsegregation of VARiants in Panel of Genes	NCT01689584	Gene Mutation-R... Genetic Predisp...	salivary kit	18 Years -	Institut Curie
Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)	NCT03075735	Prostate Cancer		18 Years - 99 Years	Centro Nacional de Investigaciones Oncologicas CARLOS III
A Study to Evaluate Rucaparib in Participants With Solid Tumors and With Deleterious Mutations in HRR Genes	NCT04171700	Solid Tumor	Rucaparib	18 Years -	pharmaand GmbH
Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)	NCT03075735	Prostate Cancer		18 Years - 99 Years	Centro Nacional de Investigaciones Oncologicas CARLOS III
Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors	NCT05169437	Solid Tumor Breast Tumor Colon Tumor, Ma... Lung Tumor Urologic Cancer Pancreatic Canc... Melanoma Metastatic Canc... Locally Advance... Esophageal Canc... Endometrial Can... Head and Neck C...	Niraparib	18 Years -	Tempus AI
Prophylactic Irradiation to the Contralateral Breast for BCAs Patients	NCT04960839	Breast Cancer	Prophylactic co...	30 Years - 70 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Prophylactic Irradiation to the Contralateral Breast for BCAs Patients	NCT04960839	Breast Cancer	Prophylactic co...	30 Years - 70 Years	Second Affiliated Hospital, School of Medicine, Zhejiang University
Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)	NCT03075735	Prostate Cancer		18 Years - 99 Years	Centro Nacional de Investigaciones Oncologicas CARLOS III
Niraparib in the Treatment of Patients With Advanced PALB2 Mutated Tumors	NCT05169437	Solid Tumor Breast Tumor Colon Tumor, Ma... Lung Tumor Urologic Cancer Pancreatic Canc... Melanoma Metastatic Canc... Locally Advance... Esophageal Canc... Endometrial Can... Head and Neck C...	Niraparib	18 Years -	Tempus AI

Spots Global Cancer Trial Database for palb2

Every month we try and update this database with for palb2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for palb2

Every month we try and update this database with for palb2 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for palb2 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.